Relapses and MS: The Importance of Rehabilitation

Learn what is going on in the central nervous system during a relapse, how different drug treatments affect a relapse and how to climb the tough road back from an attack by using rehabilitation strategies and assistive devices. This HealthTalk program is sponsored through an educational grant from MS ActiveSource.

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Trevis L. Gleason:

Dr. Frohman, let's start out with the definition of an exacerbation. What is physiologically happening inside the brain or the spinal cord of a person when they're having an MS attack or a relapse or an exacerbation, whatever we want to call that?

Dr. Elliot M. Frohman:

Well, we recognize now there are a number of different subtypes of multiple sclerosis. The most common subtype that people have is what we call relapsing-remitting MS and how most patients begin their disease. They have very specific attacks in neurologic function punctuated by a period of remission, where they have a period of recovery. Oftentimes, they're left with some degree of disability.

I think it's a misconception when we talk about relapsing-remitting MS to call it a non-progressive form of the disease. Some people accrue disability by not completely recovering from their attacks. What we mean by an exacerbation is some disruption in neurologic functioning, and it can really cut across a whole series of different domains of function for patients with MS. Virtually any neurologic symptom can potentially be caused by inflammation and changes in the brain or spinal cord. And that can include things such as visual loss, numbness, weakness, dizziness, and problems with bladder control, and, in some cases, the manifestations of an attack can be extraordinarily subtle. Some patients can have profound fatigue like nothing they've experienced before. "What is going on with me?" They aren't infected, and it's not a metabolic problem, not their glucose. It could be the manifestation of an attack.

What is going on physiologically within the central nervous system? MS is a disease of the central nervous system. This is not a disease affecting the nerves or muscle and the junction between the nerve and muscle. This is a disease that affects the brain and spinal cord. Physiologically what is happening during an exacerbation, the transmission element, the electrical wire of the nerve cell, has been in some way altered in its ability to propagate electrical signals in the brain. Here is a prime example. The ability to see something that is being processed on the retina is dependent on transmitting that visual information from the eye to the back of the brain [to] the occipital cortex where vision is processed. That process is heavily dependent on both electrical and chemical signals, and one of the properties of nerve fibers is the fact that axons, the transmission element of the nerve, is insulated with myelin. Even though myelin is a fatty substance, which is insulating and in and of itself doesn't conduct electricity, nerves have myelin, which is punctuated by small spaces where there isn't myelin. Those little nodes are where electrical messages are being transmitted from these naked areas on the axon from one area to the next. What is actually happening during an MS exacerbation? There is lots of evidence to support this now, is that cells within the immune system that normally occupy the circulation have had an increased ability to interact with the blood vessel spaces in the brain and spinal cord. Specifically what is happening is that the cells now have the ability to specifically anchor or adhere, if you will, rather than staying in the circulation, they can adhere to the blood vessel walls of the brain and spinal cord principally because of the increased manufacturing of so-called adhesion molecules, which allow those inflammatory cells to bind to the vessel wall. Once those cells bind to the vessel wall, they have the ability to move into the central nervous system and bring along with them a series of immune chemicals, which can produce things such as inflammation and edema and excessive water.

During an exacerbation when these cells are moving across the vessel wall what we also know is that the so-called blood/brain barrier, a very important specialization of the blood vessels of the brain and spinal cord, its specific function is to keep large substances out of the brain, but that blood/brain barrier during an MS exacerbation becomes leaky, and, as a consequence, there is an increased amount of tissue fluid that can get across. But when someone is having an attack, such as visual loss or inflammation in the optic nerve, we know when they go for an MRI and we introduce gadolinium - a contrast agent into the vein - this is normally a molecule that is big, bulky and stays out of the brain. In the areas of the brain where the so-called blood/brain barrier has been leaky, the gadolinium, during the MRI study can leak into the brain and tell the neurologist, radiologist and patient we can see the areas of new inflammation that is involved in an exacerbation. In conclusion, we really do know now, at least at the beginning of the disease, that inflammation is a key feature that undermines a compromise in neurologic functioning primarily related to an inappropriate or excessive migration of inflammatory cells, T cells, B cells, macrophages from the blood across the vessel walls of the brain and spinal cord and into the central nervous system tissue itself.

Trevis:

Dr. Fodor, most of us have had an attack at one point or another, and we know infused steroids are used to treat such an attack.

What are these drugs doing to the lesion, and how does it stop or slow the relapse?

Dr. Patricia A. Fodor:

Oh, the dreaded steroids - when a patient calls me and asks for steroids, I know they're feeling really bad. Generally, steroids help to decrease inflammation along the nerve, and there is also some evidence that it helps - they help to improve the nerve conduction. The steroids are helping the inflammatory cells calm down and reduce the number of cytokines and harmful substances they're producing. They also help the gadolinium - the ability for the blood/brain barrier to have absorption of the gadolinium.

Trevis:

We're reducing the inflammation on a lesion but there are a lot of side effects. When a patient calls you know they're having a hard time if they've gone through them before it is not the most pleasant of things to go through. Some patients put on significant weight. There is the steroid rage, all those kinds of things. What is happening that is causing that, for instance, the weight?

Dr. Fodor:

Well, one of the things that steroids can do is cause fluid imbalance with your electrolytes, and that can cause you to retain water. People who are on steroids, even though it's just for five days, sometimes get a very voracious appetite, particularly for carbs, and there are some elements of abdominal distension that occur with steroids. It can create weight gain, which makes everyone unhappy.

Trevis:

I know as a patient who has had steroids several times myself I'm pretty unhappy with them. I know that steroids are sometimes referred to as an emergency drug something that happens at the time of attack. I've recently heard of using Novantrone [mitoxantrone] as an emergency drug. How is it different from a steroid both chemically and how it acts on a lesion?

Dr. Fodor:

Novantrone is not being used as much in this country as it is in Europe as a first-line drug. It is a strong chemotherapeutic drug. Generally, it's an immunosuppressive drug which can, they believe, be selected for lymphocytes. It's not anti-inflammatory. It interrupts the cells during their reproduction phase.

Trevis:

Why is it being used in Europe and not here so much?

Dr. Frohman:

Their choices of therapies are somewhat more limited because of the medical systems that are there in place - the socialized medicine.

Trevis:

Finally, in this part of the discussion, I would like to ask both of Dr. Frohman and Dr. Fodor to tell us about the choice not to use a drug during an attack. I know many of our listeners try to limit the number of drugs in their systems - might not like the reaction with the steroids. When is it the right choice to take a wait-and-see attitude, Dr. Fodor?

Dr. Fodor:

Well, I think once you're sure it's a relapse, that you really need to get on something immediately. Once you're sure your symptoms aren't being caused by another problem, for example an infection or fever, if you wait, it can slow down your recovery. When you do take the steroids, you may not return to baseline as quickly, or you may not return to baseline functioning at all. You may still have some residual effects.

The wait-and-see attitude, even though on one hand you know how people dread steroids, in the long run it's probably not as good as having the treatment right away.

Dr. Frohman:

I completely agree. The first issue is as she's nicely underscored is the issue of are we dealing with an exacerbation? I think it's important for our MS patients listening to this discussion to be very clear about a very important issue of distinction, and that is that a number of exacerbations that occur during an entire year of an MS patient's life in terms of the annualized relapse rate is really only a few significant exacerbations. Whereas, people tend to have lots of physiologic fluctuation, they can have a bad day, a good day, heat- or exercise- or stress-induced worsening or return of old symptoms. The point about are you having an exacerbation, is something else going on is the first step. Certainly, we don't want to unnecessarily expose our patients to exaggerated or frequent episodes of steroid treatments even though they are very helpful. However, people in our field, there is no question that there is a different kind of behavior across neurologists. Some will say if you have a sensory exacerbation primarily involving numbness or tingling but no motor manifestations, that they oftentimes won't treat those attacks because they give them a different level of significance compared to a more disabling attack. I have to agree with Pat on this. Any new exacerbation, which we confirm is novel, is a reflection of underlying inflammation, potential tissue damage. And even though we recognize that steroids may perhaps accelerate recovery and that the outcome eventually may be similar in those patients treated with steroids or not with steroids, we now have much more confirmed evidence to suggest that tissue damage is ongoing, and steroids and other agents like chemotherapeutic agents and other therapies that we can use can substantially limit the amount of inflammatory injury that's occurring. As neurologists and patients, we have to be very careful about this idea that we should be able to see every component of an attack clinically or radiographically. We now know there is much more damage than we've previously recognized. For our practice, if we think it's a bona fide exacerbation, we think it's important to treat it not always with steroids. There are other interventions for exacerbations, but clearly steroids represent the first line and the mainstay for treating attacks for most patients with multiple sclerosis.

Trevis:

You say chemotherapy agent, steroids and other agents. What other agents might we be talking about?

Dr. Frohman:

Pat is right. Most of the mitoxantrone or Novantrone studies were done in Europe, and that may represent one of the primary reasons why there has been greater enthusiasm for it. We certainly will use drugs like Novantrone, Cytoxan [cyclophosphamide] and high-dose methotrexate - a variety of interventions in situations where patients have severe exacerbations or are not responding to steroids. As physicians and for our patients and families listening, there are a number of options. You yourself mentioned the fact that steroids are associated with lots of side effects. They can cause problems with weight gain and various issues of potential diabetes and hypertension. When we have patients who really don't tolerate steroids very well or they're diabetic and shouldn't be exposed to steroids, there are other options for treating exacerbations, which would include some of the powerful chemotherapeutic agents. We can think about things such as plasma exchange or filtering the blood, particularly when people have not responded to steroids. A lot of the anti-inflammatory strategies are used over time to decrease the risk of future exacerbations. Most neurologists that we know of will employ the use of steroids and other anti-inflammatory drugs to reduce the future risk of attacks, and that would include drugs like IVIG, (intravenous immunoglobulin). There is some data to suggest that it can reduce attacks. I use it frequently in patients who either have not done well with steroids or can't tolerate steroids, and then there are oral immunosuppressive drugs like azathioprine, mycophenolate. They go by the names of Imuran and Cellcept and even oral methotrexate. These really represent just a few of many drugs that are now emerging in our armamentarium for treating patients with MS. Perhaps we'll have a chance to discuss a few others of these new drugs that people are looking very carefully at such as Zenapax [daclizumab] and Campath [alemtuzumab]. There [is] a variety of drugs that are now available for us to treat MS patients who are having exacerbations.

We've had a relapse. We've decided with our neurologist about a drug treatment, and we've recovered to some level. Sometimes we're back to our baseline, and sometimes we have some lingering disability - now what? Dr. Weinstein, if we lose something in an attack, if we have more disability after than before, is it necessarily gone for good?

Dr. Weinstein:

No, not at all. Through rehabilitation efforts, patients can learn to compensate for lost function, substitute for lost function and enhance existing function to maximize recovery. For example, let's say with a flare or with progression of multiple sclerosis there are difficulties maintaining bladder or bowel continence. People are afraid to leave their homes because they may wet themselves or soil themselves.

These are functions that can be managed relatively easily through a variety of techniques. If through the flare-up people are having difficulties chewing or talking, then through speech pathology services improvements can be made there, and little disability remains. There can also be compensations for lost function having to do with mobility or self-care skills and even return to work that can be initiated, and in relatively short term people can return to high levels of function.

Trevis:

Can you enlighten us as to how a prescription is reached for, say, a cane versus arm crutches or a walker over a four-legged cane, etc.?

Dr. Weinstein:

The first question you have to answer is, am I having falls? If you're having even one fall, certainly more than one fall you're at tremendous risk of breaking a leg, breaking a wrist or arm, or even worse, hitting your head, which can lead to cognitive impairment. And so if a person is having falls, then an assessment of balance, coordination and strength should occur. This can be done through either a physical medicine rehabilitation doctor or physical therapist. After this evaluation, then an assessment of how one is going to use a device would be worthwhile. For example, is it going to be used only in the home, is it going to be used on sidewalks or gravel, on grass? Or will it be used even in rougher terrain? That will help to guide the level of assistive devices [that are] necessary. If there is fatigue, then maybe a power device like an electric chair or scooter would be worthwhile.

Trevis:

Sometimes the assistive device is not a temporary accessory. Sometimes it becomes more of a permanent part of the wardrobe, if you will. I know from my own experience as a patient with MS, is that we sometimes wait until, well, past the time when such aids are needed before we accept them. Dr. Fodor, how do you help your patients make and accept these difficult changes?

Dr. Fodor:

As the mother of three grown children, I never underestimate the power of guilt. I have a long talk with the patients, and we talk about their falling risk and the risk of mortality. Also, I think one of the fears people have is that people will view them differently if they use a cane or they have to use another assistive device. We talk a long time about how much more important it is for the people that love them, their families, friends, to have them around and have them functioning rather than more disabled from having a fall. I also talk about other types of therapies, such as pool therapy. People sometimes believe that once they use an assistive device it precludes them from ever having other forms of therapy. I find pool therapy to be extremely useful for my MS patients, particularly in balance issues, and also just mobility for people that are using walkers. Once they're in the water, they can walk quite well - sometimes with assistance and sometimes alone. We also talk about some other activities they may add to their regimen, such as Pilates or yoga, that provide stretching and some relief from spasticity.

Dr. Frohman:

I have to echo what Pat is saying. I would have to say my view with respect to this is very much aligned with the way physiatrists look at patients with MS. Many patients adopt a particular assistive device as a confirmation on how bad things have become, and they see themselves as being disabled and focus more on what they can't do rather than looking at the assistive device as a vehicle or a means to an end to intensify or enhance ability. So I have a very similar discussion. I think these are not short clinic visits. In taking care of patients with MS, it does require the ability to sit down, bond with the patient, to cultivate a relationship of trust and care and be willing to say things that are sometimes difficult to say and that is that.

Dr. Fodor:

And handle everyone's emotions that come up.

Dr. Frohman:

I agree. You can't do this in a short visit. The patients are going to have emotional responses. Even though you have these discussions, oftentimes the patient may not necessarily be ready. But I do think it's important when you take this history that there are falls, there is a risk of falling, to really get into this discussion as early as possible, and to try to help patients avoid something very important and that is, avoid having self-fulfilling prophecies that if I use this, I can't do other things. Emphasize the fact that the devices are vehicles, that they can continue to have a full life and a safer life and also, I think, reduce the expectation that everybody else is necessarily looking at them in a strange way. I think if you can get people over the hump at looking at themselves as doing something useful and practical that helps them live their life to the fullest with greater quality, it's a totally different perspective than focusing on what they can't do.

Trevis:

I know from my own experience at 35 years old using a cane I was pretty embarrassed but more embarrassed doing the falls and face plants.

Dr. Frohman:

The most common symptom in the MS clinic, the most common symptom is fatigue. Many patients that have spasticity, alteration in the mechanics of their walking, transfers, these are extraordinarily fatiguing experiences for these patients. I also think it merits emphasizing that using assistive devices and stretching strategies and the kinds of things I think neurologists in the know and physiatrist know all two well are aimed at reducing energy production and allow patients to have less fatigue. They're safer, and I think, ultimately, they're much more fulfilled.

Trevis:

Would you like to weigh in on this, Dr. Weinstein?

Dr. Weinstein:

Our approach is we try to encourage a safe atmosphere where the patient can talk about anything that they want to talk about. And so when we're trying to reinforce function and minimize disability, we want to be able to allow the patient to talk about anything that might be part of their fears or embarrassment. We want to find out what are their driving factors? So we'll talk about topics of work, of recreation, of sexual function, bowel or bladder management, of skin care, of mood and depression, of fatigue, of pain, whatever it takes to help a patient to help a family, to help caregivers to be able to do whatever they want to do and then to be able to show them devices such as orthotics, which help to sustain function, or assistive mobility aids to do things to reinforce what they want to do. Rather than looking at a cane as something that is a badge of disability, instead it becomes a tool of ability to maximize function.

Trevis:

We know that a healthier body will recover faster and further from a relapse. Many of us work with professional personal trainers, physical and occupational therapists, and others to help us keep what we have for as long as we can. Dr. Weinstein, can you give us some idea of the different professionals with whom you work that can help us in that recovery process? We're starting to run a little into our question and answer period, so we'll try to keep our responses brief.

Dr. Weinstein:

Thank you for the opportunity to be able to share the rehabilitation team. The functions of the team vary tremendously. In a few minutes, it would be tough to explain and share all of their different functions, but in a thumbnail sketch, a physical therapist works on strength, endurance, balance, coordination and walking abilities. An occupational therapist works on devices to enhance activities of daily living, whether it be basic activities such as grooming, dressing and bathing, or instrumental activities of daily living such as homemaking tasks and other activities around the home. The speech pathologist can work on swallowing and chewing activities as well as communication strategies and cognitive compensations. The rehabilitation psychologist can work on coping skills with chronic disease. And the recreational therapist can work on helping the patient to access their community, so that way they're not homebound, that way they can be doing things that are enjoyable, whether it be in recreation or in work.

Trevis:

That's a good point you make. A speech pathologist helps with chewing and swallowing. I know swallowing and choking can be a big issue for folks with MS. That's good to know that a speech pathologist works on that as well.

Dr. Weinstein:

It's important to maintain adequate nutrition, so that way one can minimize complications of chronic disease, including weight loss.

Trevis:

Now I have a question for Dr. Frohman. If we're in rehab and we start to experience some pain, is it our neurologist we should be checking with, doctor?

Dr. Frohman:

I would imagine that any member of the multidisciplinary team should be consulted when pain becomes an issue and certainly in the rehabilitation setting. Pain can be derived from issues related to MS, so it could be neuropathic or derived from lesions within the brain or spinal cord. It could be musculoskeletal discomfort related to remobilizing a limb, which may be spastic. There may be pain issues related to skin integrity. They may be using things in a way they haven't used them before. I think all members of the team, including the physicians, physiatrist, neurologist and certainly the physical and occupational therapist [should be involved], everyone involved in working with the patient. If pain is occurring, then I think that's the time to bring it up and begin to focus on trying to characterize the pain. When does it occur? What is the character and quality, what brings it on and what mitigates it? All the members of the team, I think, are really useful to confer with about this. But, of course, the issue of intervening with a prescription or treatment for pain certainly is under the purview of the neurologist, physiatrist and internist, and gynecologist, and everybody involved with the patient.

It depends on when it's occurring and who we're interacting with at that time.

Trevis:

We've been talking a lot about fatigue and using assistive devices to ease it and talk about an energy budget. [We've talked about] how the use of the proper mobility aids and exercise, how that can help us not only conserve the energy that we have for the things we want to do but maybe even actually decrease fatigue and increase the energy that we have to spend in that budget.

Dr. Fodor:

[It] used to be that when a patient was diagnosed with MS, they were told to go home and rest because they would deplete the energy. There was only so much that people were given. If you used it up, you didn't get any back. I find through PT and the use of assistive devices people can create a reserve so that if they have a relapse, it isn't quite as bad. They have something to draw on. In my clinical experience, I see that people who concentrate on core strengthening and balance improvement actually do a lot better. You expend a lot of energy if you don't know how to transfer right, if you are having difficulty walking, if you are maintaining energy to try to keep yourself upright and balanced. So I think that all these things together and used properly and taught along with energy conservation techniques can really improve the quality of life.

Caller:

Yes, I would like to know that once you have a relapse or an exacerbation, how soon you should resume exercise if you have exercised regularly.

Dr. Weinstein:

Exercise like lifting weights we would not encourage right away. We would encourage instead the resumption of activities of daily living and after they have been done on a consistent basis, then gradually increasing activity to incorporate a formal exercise program. A range of motion, of course, can be done without great energy expenditure but riding on the last question you had we would certainly be promoting pacing and if you could get down the concept of pacing well, that is doing activity, taking a break, doing an activity again and taking a break, then exercise fits very well into that pattern.

Trevis:

Thank you, doctor. I would like Dr. Fodor to field this one. It comes from Colleen. I've started to notice some cognitive changes. I can't think of words, spelling issues, wrong spoken words, etc. Is there any rehabilitation for this?

Dr. Fodor:

In our clinic, we have found speech therapy usually handles cognitive rehabilitation issues, and we start off usually by suggesting aids that can be used to help you remember things. For example, there are inexpensive recorders you can get from Radio Shack making lists, using stickies, which people use anyway. And then there is an actual cognitive program, which we're trying to get adapted to where the speech therapist will train the patient and the exercises are practiced at home, and it has been shown to make a substantial difference in cognitive issues. We consider drug therapy, and I have put some patients on Aricept [donepezil] and Reminyl [galantamine] - both drugs used for dementia. We have to take into consideration that cognitive decline can be caused by depression. It's one of the worst influences on your memory and that should be treated first before we add any other therapies.

Caller:

How do you know when you've gone for the relapsing-remitting to the progressive-secondary?

Dr. Frohman:

It's a great question. There is, in general, no exact specific line that you pass in terms of milestones to really detect that. But clearly, we do recognize that the early phase of multiple sclerosis is more characterized by specific attacks, which tend to come on relatively abruptly followed by some degree of recovery followed usually by a free period that we call a remission, and that's why we call it relapsing-remitting MS. What's different about secondary-progressive MS is patients begin to note a very slow, kind of insidious change, and they don't fully perceive it. It is not clear to them that they're worsening until they begin to see an impact over time on their activities of daily living - their walking speed, the time it takes to get dressed, issues related to dexterity, cognitive problems. Aand then later it becomes much more conspicuous rather than inconspicuous, and people will begin to say, "I'm having a fairly steady decline in my ability to walk, my balance mechanisms are different. I'm having more problems with bladder control." What differentiates the early relapsing-remitting phase from the so-called secondary-progressive phase of the disease is patients with secondary-progressive disease seem to have a slow almost insidious progressive change over time.

They can have periods of stability, followed by further progression. But it is really a question of pace. Whereas, the relapsing-remitting patients have more abrupt, acute events followed by remission.

Pathologically, we think the two phases of the disease may be different as well. Specifically, the relapsing-remitting phase of the disease appears to be more about inflammation and attacks and new lesions whereas the progressive phase of the disease, whether it's secondary-progressive MS or primary-progressive MS, we think that pathology is more about degeneration of the nerve fibers. They seem to be somewhat different clinically in the way they look but also pathologically. My final point is that there is really strong evidence that controlling the early phase of the disease, the inflammatory phase, may actually be somewhat protective, if you will, neuroprotective against the later degeneration that occurs. Certainly, we want to hope that our therapies for the future will be more robust, more effective, and that we can identify people even earlier and earlier for that more robust therapy in order to prevent a conversion from a relapsing to progressive form of the illness.

Trevis:

How can you tell if you're having a relapse?

Dr. Fodor:

I usually tell patients that if they have symptoms that are disabling to them, whether they're sensory or more obvious like weakness or trouble walking that persist for more than 24 to 48 hours, it's time to call me.

Trevis:

Our next question is from the Internet, Kathy in Hollywood, Florida, "Why does the summer heat make my MS worse?"

Dr. Fodor:

I think what is happening is the heat is disrupting the nerve conduction, and that seems to affect people very specifically. I find in my patients that I have some that are quite affected by the heat but others that aren't bothered it at all. Elliott, what do you think?

Dr. Frohman:

I agree. In fact, most patients, if they have some kind of thermal sensitivity tend to be heat-sensitive. You're right. I have patients with no difficulty with the heat. They enjoy the heat and will take a hot shower, and correspondingly there are a few patients, some patients, who are more cold-intolerant than heat-intolerant with their MS. I would reiterate again that most of the suffering and difficulty that patients have day to day are not the attacks because attacks are not occurring day to day. It is typically not the disability because it takes time for disability to occur, and certainly that can play a major role in patients suffering with the disease, but the major day-to-day, hour-to-hour, minute-to-minute change has to do with things like temperature change, exercise, psychological stress, a good day or bad day. Those factors seem to work with the path of physiology with MS, which is demyelenation. And when the myelin comes off the nerve fiber, it's subject to changes in the electrical-conducting properties of the nerves.

It doesn't make much for patients to electrically go over the edge, and the nerves may not work at all.

One of the most important areas of new research for novel therapeutics is to focus specifically on how can we enhance the physiology of the nerves minute to minute, hour to hour so while we're working on therapies to attack progression patients could be about the same at 4:00 or 5:00 in the afternoon compared to 8:00 in the morning. I think it's a very important area in helping us better manage our patients.

Dr. Weinstein:

One can learn to beat the heat, too, that is by organizing their day around the afternoon, that is trying to do more activities during the cooler parts of the day or the evening, that is minimizing activities outside of the home or even use of a cooling jacket when one goes outside.

Trevis:

Are you using cooling therapies of any sorts during rehab?

Dr. Weinstein:

During therapy, we're in an air-controlled area so that's not a problem but pacing oneself on hot days, trying to stay adequately hydrated, trying to use fans and adequate ventilation to avoid getting overheated, and, of course, as I've just mentioned trying to organize the day around the heat cycles.

Dr. Frohman:

If I could intervene one second, I think Dr. Weinstein's point is excellent, and the point about the cooling jackets is great. If you find that you have patients that respond to these cooling jackets, it can be a lifesaver to those patients, and stores like Brookstone and the Sharper Image have a number of regional cooling devices, a fan you wear around your neck or a cooling wristband or headband, use of ice-cold liquids. A variety of these very simple procedures can really make the difference between being able to do something and not do something at all. I think it's very, very important to be aware of some of these strategies that can actually help optimize the electrical abilities of the nerves, no question.

Trevis:

I think it's also important for everyone to note some of these cooling vests, air conditioners can be expensive. And if folks are on Social Security and disability, etc., it can be a burden. I know your local chapter of the National Multiple Sclerosis Society might be able to help there as well.

Caller:

How can you avoid constipation, chronic constipation and swelling?

Dr. Fodor:

I usually recommend my patients stay very hydrated. It is so dry here in Colorado. Eat fruits, vegetables and use fiber in their diet, then, of course, if that doesn't work, you can progress onto stool softeners and other agents that we can use to keep people well-lubricated and going. I think I would pass that on to Dr. Weinstein to see if he has any other ideas.

Dr. Weinstein:

There are many simple preparations over the counter that can help with mobility whether they be supplemental fiber agents to the diet or agents that help to hold fluid into the bowels. But if that's not useful, then using other products such as low-dose Milk of Magnesia, Dulcolax tablets, the use of gentle suppositories like glycerin suppositories or stronger ones such as the mini-enemas. We usually want to help people to time their bowel movements based upon what their patterns have been in the past and to do it in conjunction with a meal. And it's important that everybody recognize that a bowel movement has a varying frequency in the population. Some people don't feel comfortable unless they're having a bowel movement every day. Other people feel comfortable every other day or every third day. And so we want to establish a pattern that works well for an individual and for care providers, also to allow people to get outside of the home.

Trevis:

Thank you to both of you. Our next question is on the Internet from Cheri in Nebraska. She says, "I took two doses of Tysabri.

Both myself and my neurologist think I've improved on the medication, and I can't have any more infusions. I've heard rumor it may be available down the road." Is it true, Dr. Frohman?

Dr. Frohman:

Tysabri [natalizumab] is a novel drug that specifically interrupts the process by which inflammatory cells become attached to the blood vessel wall. But Tysabri is really an amazing drug primarily, I think, because it's really a derivative of evidence-based medicine and proposing a hypothesis on how inflammation occurs in adhesion and then developing a drug that can interrupt that process. That being said, the clinical trials have shown that Tysabri is the most effective therapy on the planet earth for multiple sclerosis that has a dramatic reduction in new brain lesions, a dramatic reduction in exacerbations and we know even a reduction in progression of disability and also a reduction in the most injurious brain lesions that occur on MRI. That being said, during the clinical trials, specifically in the trial where it was combined with weekly Avonex, a form of interferon beta, two patients developed a very serious infection called PML caused by a JC virus. We had many patients in the trial. Dr. Fodor was involved in the trial as well. I still think it represents an extremely important strategy. What we need to understand is why did these infections occur in these two MS patients? One patient with Crohn's disease involved in a trial also got the infection. My feeling is that this drug coming back to market has to be done in such a way that we as physicians, along with our patients and families, will have some kind of surveillance strategy to determine who is at-risk, when they're at-risk, what are we going to do if an infection arrives, and can we treat an infection or immunize patients against this particular viral family so this infection doesn't occur? I think it has to occur before we can bring this drug back to market and shoot the dice and take the risk without knowing more about the biology of what happened in these three patients.

Trevis:

I know that most of the patients it occurred at the very end of the trial. Is it possible maybe that this drug is going to have a maximum dosage over the lifetime like Novantrone does because of the cardiotoxicity?

I don't think so. I think if you look at the data in the patient with Crohn's disease, this was a patient who had previously been treated with a number of other immune-modulating drugs such as azathioprine and a rheumatoid arthritis drug used in Crohn's called infliximab [Remicade]. It turns out that, very interestingly, that patient had blood samples banked periodically throughout the course of that person's participation in multiple clinical trials. It turns out in that patient when Tysabri was started, shortly after starting the drug, one can see the conversion from the blood being negative for the virus to being positive. So I don't think it's an issue of just exposure. It may have something to do with do some people have a more aggressive form of the virus than others? I think our listeners need to understand most people walking the planet have JC virus in their bone marrow and in their kidneys. It's just our immune systems are so professional that the virus doesn't have a chance to take hold. This is a very rare infection. Is there something different or unique about these three patients? Was there something unique about the particular form of JC virus that they had, or was it the fact that Tysabri was used in the context of patients having received other drugs that also modulate the immune system?

My final point would be if Tysabri is the best drug on the planet earth, could it be that when combining it with other drugs the therapy may be too good? And we may in some way compromise or cripple some very basic surveillance functions that our immune system really has to provide including allowing some cells to get into the brain and spinal cord to perform those kind of housekeeping functions to makesure that infections don't arise.

Caller:

What's the most effective exercise for improving balance and reducing stiffness?

Dr. Weinstein:

That's a great question. There is no one simple answer for that. It really depends on your pattern of weakness and your pattern of control. It also would have to do with your ability to manage your tone, which is sideways of talking about a condition called spasticity. So there are a variety of exercises. There are a variety of positioning strategies that can be useful, but it would require a bit more assessment to give a more specific answer.

Trevis:

Joni in California has e-mailed us a question that might be a good follow-up for that, "Is it true that new neuropathways can be formed by exercising weakened muscles?"

Dr. Weinstein:

It's another great question and a controversial one. Is it new neuropathways or is it use of other ones in a better strategy or compensatory way? I think there is evidence in the literature for both. But rather than argue over it, we want to have people demonstrate improvement through these strategies.

Caller:

I was wondering why it seems that relapses that are cognitive take longer to recover from than relapses that are physical.

Dr. Frohman:

That may be the listener's impression, but patients are highly varied with multiple sclerosis. It may be that when patients have a relapse predominantly affecting their cognitive capabilities, there may be other factors at play such as there could be depression. I know Dr. Fodor mentioned this before.

Depression is the most common treatable cause of cognitive impairment on the planet unless you want to consider the fact that Alzheimer's is increasingly becoming more treatment-sensitive, but certainly depression and disorders of mood can play a role with that. That in context with cognition, people can be depressed about their exacerbation. There may be other factors.

Trevis:

We have an e-mail question from Denise in Ohio, "Please discuss the benefits of prescribed physical therapy over a personal exercise program without supervision." Dr. Weinstein, can you take that one?

Dr. Weinstein:

The risk of a personally directed exercise program is that it may not be the most beneficial for trying to maintain symmetry of muscles, trying to encourage pacing or looking at maximizing of the function of strong muscles, and trying to adequately strengthen weak muscles. If muscles are also extremely weak, then exercise might even promote more fatigue. So there is also the risk of exercise damaging joints and contributing to pain that would further impair mobility and activity and sleep. So a guided exercise program would certainly be worthwhile. This doesn't mean that you have to go to a physical therapist to exercise in front of them. But a physical therapist can provide information that could be then utilized in a variety of settings, whether it be a home or a gym or a pool, in order to help you to be able to exercise but in a fun way, so you don't have to feel like it's a chore and to be able to maximize your function. If the exercise is focused toward the activity you want to do, then it will be not only more consistently be done, but you'll get greater benefits from that.